WEEKLY IMPORTANT NEWS FROM MEDSCAPE AND OTHER SOURCES
Τετάρτη, 25 Νοεμβρίου 2015
NIVOLUMAB APPROVED FOR MELANOMA BY FDA
The U.S. Food and Drug Administration (FDA) today approved the programmed cell death protein 1 (PD-1) inhibitor nivolumab (Opdivo) as a single agent for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma.
Clinical Trial Results
The approval is based on data from the phase III CheckMate 066 trial of treatment-naive patients with unresectable or metastatic BRAF wild-type melanoma who were randomly assigned to receive nivolumab or dacarbazine. The primary endpoint of the trial was overall survival, and secondary endpoints were progression-free survival and objective response rate.
Nivolumab demonstrated superior overall survival vs chemotherapy in the first-line setting. Results were based on the analysis conducted on 47% of the total planned events for overall survival. The median overall survival was not reached for nivolumab and was 10.8 months (95% confidence interval [CI] = 9.3–12.1) in the dacarbazine arm (hazard ratio [HR] = 0.42, 95% CI = 0.30–0.60, P < .0001).
Median progression-free survival more than doubled with nivolumab: 5.1 months vs 2.2 months for patients treated with dacarbazine (HR = 0.43, 95% CI = 0.34–0.56, P < .0001). Objective response rate with nivolumab was 34% compared to 9% with dacarbazine. At the time of analysis, 88% nivolumab-treated patients had ongoing responses, which included 43 patients with ongoing responses of 6 months or longer.
In the trial, serious adverse reactions occurred in 36% of patients receiving nivolumab. Grade 3 and 4 adverse reactions occurred in 41% of patients receiving nivolumab, the most frequent being gamma-glutamyl transferase increase (3.9%) and diarrhea (3.4%). Adverse reactions led to permanent discontinuation of nivolumab in 7% of patients and dose interruption in 26% of patients.
The most common adverse reactions in CheckMate 066 (> 20%) reported with nivolumab vs dacarbazine were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%).
Nivolumab is associated with immune-mediated adverse reactions including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, rash, and encephalitis; infusion reactions; and embryofetal toxicity.